Project Summary Over 30 million people are currently infected with HIV, and over 2 million people die from AIDS each year. These numbers are dwarfed only by the number of individuals infected with tuberculosis (TB). Approximately two-thirds of the world's population is currently infected with the bacterium that causes TB, and approximately 10% of those individuals develop active TB. Individuals who are infected with both HIV and TB are up to 31 times more likely to develop tuberculosis than those with TB alone. Thus, there is an inherent need to understand how HIV affects the immune response to TB and whether an intervention can be designed to prevent tuberculosis in co-infected individuals. We have recently identified two unique populations of non- classical CD8+ T cells in rhesus macaques that we believe are critical players in anti-mycobacterial immunity: mucosal associated invariant T cells (MAITs), and MHC-E restricted CD8+ T cells. Thus, the goal of this proposal is to characterize these unique T cells following BCG vaccination and understand how SIV infection impacts their anatomical distribution and function.